This is an application for an NIMH Mentored Patient-Oriented Research Career Development Award (K23). The candidate's interest is in the early identification and treatment of schizophrenia. He has previously conducted research in the phenomenology and early clinical course of schizophrenia. This career development program will allow him to pursue 1) specialized training in the methods of early detection in schizophrenia, and 2) training in the procedures necessary to conduct genotype-phenotype association analyses. Training will include individual mentoring by experts in schizophrenia research and molecular genetics at the University of Iowa, as well as training at the laboratories of external consultants who are leading the research in schizophrenia prevention. The training program will also be closely integrated with a research plan focusing on the investigation of two candidate genes (brain-derived neurotrophic factor (BDNF) and Disrupted-in-Schizophrenia 1 (DISC1)) and their relationships with two quantitative phenotypes of schizophrenia (neurocognitive dysfunction and MRI brain volume deficits). The aims of the research plan are 1) to identify neurocognitive and MRI brain morphometric correlates of BDNF and DISC1, and 2) to study neurocognitive dysfunction and structural brain deficits in unaffected siblings of schizophrenia probands. This integrated career development program, providing training in high-risk research methodology, molecular genetics, cognitive neuroscience and biostatistics, will enhance the candidate's ability to combine biological (e.g. endophenotypic traits, genetic variations) and clinical (e.g. prodromal symptoms, familial history) risk factors into multi-stage screening programs for the early identification of schizophrenia. Taken together, the training program and research plan provide the potential for scientific discovery as well as support for the establishment of an independent research career.